› 3um5

X-ray diffraction
2.4Å resolution

Double mutant (A16V+S108T) Plasmodium falciparum dihydrofolate reductase-thymidylate synthase (PfDHFR-TS-T9/94) complexed with pyrimethamine, NADPH, and dUMP

Released:
DOI: 10.2210/pdb3um5/pdb
PDB entry 3um5 coloured by chain, front view.
PDB entry 3um5 coloured by chain, side view.
PDB entry 3um5 coloured by chain, top view.
Source organism: Plasmodium falciparum
Primary publication:
Combined spatial limitation around residues 16 and 108 of Plasmodium falciparum dihydrofolate reductase explains resistance to cycloguanil.
Vanichtanankul J, Taweechai S, Uttamapinant C, Chitnumsub P, Vilaivan T, Yuthavong Y, Kamchonwongpaisan S
Antimicrob Agents Chemother 56 3928-35 (2012)
PMID: 22526319

Function and Biology Details

Reactions catalysed: 
5,6,7,8-tetrahydrofolate + NADP(+) = 7,8-dihydrofolate + NADPH
5,10-methylenetetrahydrofolate + dUMP = dihydrofolate + dTMP
Biochemical function:
Biological process:
Cellular component:
Sequence domains:

Structure analysis Details

Assembly composition:
homo dimer (preferred)
Assembly name:
PDBe Complex ID:
PDB-CPX-108405 (preferred)
Entry contents:
1 distinct polypeptide molecule
Macromolecule:
Bifunctional dihydrofolate reductase-thymidylate synthase Chains: A, B
Molecule details ›
Chains: A, B
Length: 608 amino acids
Theoretical weight: 71.87 KDa
Source organism: Plasmodium falciparum
Expression system: Escherichia coli
UniProt:
  • Canonical: A7UD81 (Residues: 1-608; Coverage: 100%)
Gene names: DHFR-TS, dhfr-ts
Sequence domains:
Structure domains:

Ligands and Environments


Cofactor: Ligand NDP 2 x NDP
2 bound ligands:
Ligand CP6 2 x CP6
Ligand UMP 2 x UMP
No modified residues

Experiments and Validation Details

Entry percentile scores
X-ray source: ENRAF-NONIUS FR591
Spacegroup: P212121
Unit cell:
a: 56.529Å b: 155.119Å c: 165.257Å
α: 90° β: 90° γ: 90°
R-values:
R R work R free
0.202 0.202 0.254
Expression system: Escherichia coli

Quick links

Citations

3 review citations

Folate metabolism in human malaria parasites--75 years on.
Müller et al. (2013)
2 more

1 mention without citation

Combined spatial limitation around residues 16 and 108 of Plasmodium falciparum dihydrofolate reductase explains resistance to cycloguanil.
Vanichtanankul et al. (2012)